The primary goal of the project is to determine if specific immunological tolerance to genetically mismatched heart allografts in rhesus monkeys can be achieved. Two approaches are being undertaken. In the first approach, the hosts are exposed to the antigens of the cardiac allograft donors after their immune systems have been rendered immature with total body irradiation and lymphocyte-depleted marrow reconstitution. As the immune systems relearn to distinguish "self" from "foreign" antigens, they may recognize the alloantigens as "self" and accept the grafts. In the second approach, the hosts are transformed into radiation chimeras by lymphocyte-depleted marrow transplants following total body irradiation. The long-term presence of the donor bone marrow cells in the host should result in acceptance of the cardiac allografts. However, graft-vs-host disease may be a major problem in the hosts. Bone marrow lymphocyte depletions are performed with complement-mediated lysis in the presence of a panel of mouse anti-human-lymphocyte monoclonal antibodies known to cross-react with rhesus lymphocytes.